title: Predicting drug hydrolysis based on moisture uptake in various packaging designs.
abstract: An attempt was made to predict the stability of a moisture sensitive drug product based on the knowledge of the dependence of the degradation rate on tablet moisture. The moisture increase inside a HDPE bottle with the drug formulation was simulated with the sorption-desorption moisture transfer model, which, in turn, allowed an accurate prediction of the drug degradation kinetics. The stability prediction, obtained by computer simulation, was made in a considerably shorter time frame and required little resources compared to a conventional stability study. The prediction was finally upgraded to a stochastic Monte Carlo simulation, which allowed quantitative incorporation of uncertainty, stemming from various sources. The resulting distribution of the outcome of interest (amount of degradation product at expiry) is a comprehensive way of communicating the result along with its uncertainty, superior to single-value results or confidence intervals.
authors.affiliation: Lek Pharmaceuticals d.d., Sandoz Development Center Ljubljana, Verovskova 57, SI-1000 Ljubljana, Slovenia. klemen.naversnik@volja.net
authors.forename: Klemen
authors.initials: K
authors.lastname: Naversnik
authors.forename: Simona
authors.initials: S
authors.lastname: Bohanec
mesh_terms: D003198:Computer Simulation; D004349:Drug Packaging; D004355:Drug Stability; D004356:Drug Storage; D005544:Forecasting; D006813:Humidity; D006868:Hydrolysis; D007700:Kinetics; D015233:Models, Statistical; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012996:Solutions; D013696:Temperature; D013816:Thermodynamics; D014867:Water
chemical_list: D004364:Pharmaceutical Preparations; D012996:Solutions; D014867:Water